Substituted cinnamyl-2,3-dihydrobenzofuran and analogs useful as anti-inflammatory agents
AssigneeMerck & Co., Inc.
InventorsMichael N. Chang, Milton L. Hammond, Norman P. Jensen, John McDonald, Robert A. Zambias
Life of this patent
Estimating the term…
Abstract
Substituted cinnamyl-2,3-dihydrobenzofurans and analogs were prepared from the nucleophilic substitution of a cinnamylhalide with a 2,3-dihydrobenzofuran anion or an analog thereof. These compounds were found to be potent topical anti-inflammatory agents.
Claims12
A compound of formula (I) or (II) ##STR4## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3
- A is
- (a) phenyl substituted with (R.sup.1).sub.q wherein when q is 2 to 5 R.sup.1 can be the same or different from each other and R.sup.1 is
- (1) hydrogen;
- (2) halo;
- (3) loweralykoxy;
- (4) lower alkylthio;
- (5) lower alkyl sulfinyl;
- (6) lower alkyl sulfonyl;
- (7) unsubstituted or substituted phenyl loweralkoxy;
- (8) loweralkyl;
- (9) loweralkenyl;
- (10) lower alkanoyl;
- (11) haloloweralkyl;
- (12) --COOH;
- (13) aryl;
- (14) aryloxy;
- (15) cyano;
- (16) hydroxyloweralkyl;
- (17) halo loweralkanoyl;
- (18) heteroaryl as defined below;
- or
- (19) loweralkanoyloxy;
- q is 0 to 5;
- (b) unsubstituted or substituted heteroaryl selected from a group consisting of:
- (1) thienyl;
- (2) benzothienyl;
- (3) furyl;
- (4) benzofuryl;
- (5) pyrryl;
- (6) indolyl;
- (7) thiazolyl;
- (8) benzothiazolyl;
- (9) thiadiazolyl;
- (10) benzothiadiazolyl;
- (11) quinolyl;
- (12) isoquinolyl;
- (13) pyridyl;
- (14) pyrazinyl;
- (15) tetrazolyl;
- or
- (16) triazolyl,
- the heteroaryl above being substituted with one or more of R.sup.1.
A pharmaceutical composition for treating topical inflammation comprising a pharmaceutical carrier and an effective amount of a compound of formula (I) or (II) ##STR6## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3
- A is
- (a) phenyl substituted with (R.sup.1).sub.q wherein when q is 2 to 5 R.sup.1 can be the same or different from each other and R.sup.1 is
- (1) hydrogen;
- (2) halo;
- (3) loweralkoxy;
- (4) lower alkylthio;
- (5) lower alkyl sulfinyl;
- (6) lower alkyl sulfonyl;
- (7) unsubstituted or substituted phenyl loweralkoxy;
- (8) loweralkyl;
- (9) loweralkenyl;
- (10) lower alkanoyl;
- (11) haloloweralkyl;
- (12) --COOH;
- (13) aryl;
- (14) aryloxy;
- (15) cyano;
- (16) hydroxyloweralkyl;
- (17) halo loweralkanoyl;
- (18) heteroaryl as defined below;
- or
- (19) loweralkanoyloxy;
- q is 0 to 5;
- (b) unsubstituted or substituted heteroaryl, selected from a group consisting of:
- (1) thienyl;
- (2) benzothienyl;
- (3) furyl;
- (4) benzofuryl;
- (5) pyrryl;
- (6) indolyl;
- (7) thiazolyl;
- (8) benzothiazolyl;
- (9) thiadiazolyl;
- (10) benzothiadiazolyl;
- (11) quinolyl;
- (12) isoquinolyl;
- (13) pyridyl;
- (14) pyrazinyl;
- (15) tetrazolyl;
- or
- (16) triazolyl,
- the heteroaryl above being substituted with one or more of R.sup.1.
A method of treating or decreasing topical inflammation comprising the administration to a mammalian species in need of such treatment a therapeutically effective amount of a compound of formula I or II ##STR8## or a pharmaceutically acceptable salt thereof wherein n is 2 or 3
- A is
- (a) phenyl substituted with (R.sup.1).sub.q wherein when q is 2 to 5 R.sup.1 can be the same or different from each other and R.sup.1 is
- (1) hydrogen;
- (2) halo;
- (3) loweralkoxy;
- (4) lower alkylthio;
- (5) lower alkyl sulfinyl;
- (6) lower alkyl sulfonyl;
- (7) unsubstituted or substituted phenyl loweralkoxy;
- (8) loweralkyl;
- (9) loweralkenyl;
- (10) lower alkanoyl;
- (11) haloloweralkyl;
- (12) --COOH;
- (13) aryl;
- (14) aryloxy;
- (15) cyano;
- (16) hydroxyloweralkyl;
- (17) halo loweralkanoyl;
- (18) heteroaryl as defined below;
- or
- (19) loweralkanoyloxy;
- q is 0 to 5;
- (b) unsubstituted or substituted heteroaryl, selected from a group consisting of:
- (1) thienyl;
- (2) benzothienyl;
- (3) furyl;
- (4) benzofuryl;
- (5) pyrryl;
- (6) indolyl;
- (7) thiazolyl;
- (8) benzothiazolyl;
- (9) thiadiazolyl;
- (10) benzothiadiazolyl;
- (11) quinolyl;
- (12) isoquinolyl;
- (13) pyridyl;
- (14) pyrazinyl;
- (15) tetrazolyl;
- or
- (16) triazolyl,
- the heteroaryl above being substituted with one or more of R.sup.1.
Dependencies are inferred from the claim text.